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Liver Disease

Liver Disease. Thomas C Sodeman MD FACP Associate Professor of Medicine Chief, Division of Hepatology University of Toledo. Liver Disease. Approach to abnormal labs AST ALT Alkaline phosphatase Bilirubin. Liver Disease. Laboratory patterns Hepatitis AST/ALT//Alkaline phosphatase

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Liver Disease

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  1. Liver Disease Thomas C Sodeman MD FACP Associate Professor of Medicine Chief, Division of Hepatology University of Toledo

  2. Liver Disease • Approach to abnormal labs • AST • ALT • Alkaline phosphatase • Bilirubin

  3. Liver Disease • Laboratory patterns • Hepatitis • AST/ALT//Alkaline phosphatase • Cholestatic • Bilirubin/alkaline phosphatase//AST/ALT

  4. Liver Disease • Laboratory patterns • Hepatitis • AST/ALT < 1000 viral • Hepatitis • AST/ALT > 5000 fulminant hepatitis

  5. You are seeing a 24 year old male to establish care. He states he has had no medical issues, but has noticed his eyes will turn yellow when he has a cold. He is concerned that he may develop cirrhosis like his father, who drank heavily. He is on no medications, and his examination is normal. His total bilirubin is 2.3 mg/dL, direct bilirubin 0.2 mg/dL. Your next evaluations should be: • Reassurance • CT scan of the liver • Hepatitis serologies • Liver biopsy • HFE gene study

  6. Liver Disease • Hyperbilirubinemia • Unconjugated – increased production • Hemolysis • Conjugated - dysfunction • Gilbert’s syndrome • Elevated total bilirubin – unconjugated • Fasting / illness

  7. You are asked to see a 67 year old male found at home and hospitalized. He has a past history of hypertension and dementia. His diet recently had consisted of only prune juice and celery. He is disheveled looking, emaciated, and has multiple bruises on his upper and lower extremities. His labs show an albumen of 1.3, normal transaminases, a microcytic anemia, and an INR of 2.5. He takes no medications at home. Your next step to evaluate his elevated INR would be: • Hepatitis serologies • Ceruloplasmin • Ultrasound of the liver • Vitamin K supplementation • Liver biopsy

  8. Liver Disease • Measures of synthetic function • Short term • PT/INR • Longer term • Albumen

  9. Liver Disease • Measures of synthetic function • INR elevation due to malabsorption vs. dysfunction • Malabsorption responds to vitamin K

  10. Liver Disease • Other evaluations • Radiologic • Pathologic • Functional • HIDA

  11. Liver Disease • Radiologic • Ultrasound – masses, flow, fat • CT – masses, fat • MR – masses, fat • PET – malignancy • ERCP – ‘plumbing’

  12. Liver Disease • Pathologic • Diagnosis – used when labs / imaging unclear • Staging – degree of fibrosis – important for treatment decisions and prognosis

  13. Your patient, a 25 year old female, just returned from a vacation in Mexico a month ago. Recently she has been feeling fatigued, and has had modest right upper quadrant discomfort. Yesterday she noticed that her eyes were yellow. Past medical history is significant for asthma, current medication is an inhaler. Physical exam reveals scleral icterus, and a slightly enlarged liver. Laboratories show an INR of 1.0, AST 450 U/L, ALT 435 U/L, and bilirubin of 3.2 mg/dL. Your next evaluation would be: • Intravenous immunoglobulin • Referral for liver transplantation • Referral for alcohol treatment • Lamivudine 100mg po QD • HAV IgM

  14. Liver Disease • Hepatitis A • Incubation 2-6 weeks • Fecal oral • IgM anti HAV • No treatment • No chronic condition • Ig for contacts • Vaccine for travelers

  15. Your patient comes in with jaundice. He is a 30 year old male with a history of intravenous drug abuse. He has not recently traveled, and drinks 2 to 3 beers a day. On examination he has scleral icterus and jaundice, no asterixis, no ascites or edema, and no stigmata of chronic liver disease. Past screening has been negative for viral hepatitis, and past medical history is unremarkable. Labs show as AST of 1000 U/L, ALT 1200 U/L, alkaline phosphatase of 150 U/L, total bilirubin of 3.0 mg/DL, and an INR of 1.2. Your next step should be: • Referral for liver transplantation • CT scan of the liver • Hepatitis serologies • Liver biopsy • Lamivudine 100 mg PO QD

  16. Liver Disease • Hepatitis B • Incubation 4 – 24 weeks • Parenteral • HBsAg, HBsAb • HB core Ab • HB e Ag, Ab • HBV DNA

  17. Liver Disease

  18. Your patient comes for evaluation of her chronic hepatitis. She is a 53 year old nurse who contracted hepatitis B via a needle stick. She does not drink alcohol, and has well controlled hypertension. Examination is normal, labs show AST and ALT twice normal, and HBV DNA PCR shows 1,300,000 copies / mL. Liver biopsy showed minimal fibrosis and moderate portal and parenchymal inflammation. Your next step would be: • Reassurance • CT scan of the liver • Referral for liver transplantation • Tenofovir • Repeat liver biopsy in one year

  19. Liver Disease • Hepatitis B • Fulminant • Initial or reactivation • Chronic • Cirrhosis • Hepatocellular carcinoma

  20. Liver Disease • Hepatitis B • Treatment • Evidence of inflammation (biopsy, enzymes) • Elevated DNA (<10000 copies / mL)

  21. Liver Disease • Hepatitis B • Treatment • Interferon – not in cirrhosis • Lamivudine - resistance • Adefovir • Entecavir

  22. Your patient presents for further evaluation of hepatitis C found at blood donation. He is a 54 year old male in otherwise good health, and his route of acquisition is a transfusion at age 10. His examination is normal, labs show AST and ALT 1.5 times normal, genotype of 1a, and a viral load of 2,300,000 IU/mL. Testing at donation showed a viral level of 1,400,000 IU/mL 4 months ago. Your next step is: • Pegylated interferon and ribavirin • CT scan of the liver • reassurance • Liver biopsy • HFE gene study

  23. Liver Disease • Hepatitis C • Incubation 2-10 weeks • Parenteral • Pre late 1980’s – transfusion / IVDU • Now - IVDU

  24. Liver Disease • Hepatitis C • Diagnosis • Initial – anti HCV • Confirmation – RNA PCR – not RIBA • Additional – genotype, viral load • Biopsy – long duration, duration unknown, confounding factors (alcohol)

  25. Liver Disease • Hepatitis C • Treatment • Stage ≥2 • Not viral load • Interferon / ribavirin • Length depends upon genotype • 1 – 48 weeks • 2,3 – 24 weeks

  26. Liver Disease • Hepatitis C • Treatment • Side effects • Depression – (suicide) • Fatigue • Aches • Cytopenias (RBC / WBC / plt) • Thyroid • Hair loss • Weight loss

  27. Liver Disease • Hepatitis C • Treatment • Reasons to stop treatment • Suicidal ideation • No response at 3 months (2 log drop viral load) • Intolerance of side effects • Not cytopenias unless severe • First try growth agents • PLT < 10,000 • ANC <750 • Severe anemia

  28. Liver Disease • Hepatitis D • Incubation 4-24 weeks • Parenteral - IVDU • Coinfection • Superinfection • Treat HBV

  29. Liver Disease • Hepatitis E • Incubation 2 – 9 weeks • Parenteral • Rare in US • Similar to HAV • 20% mortality in pregnancy

  30. Liver Disease • CMV • EBV • HZV - pregnancy • Adenovirus

  31. Your patient presents for evaluation of fatigue, She is a 65 year old retired teacher with a past medical history of hypothyroidism and hypertension, under control. Examination reveals slight hepatomegaly and 1+ pitting edema at the ankles. Laboratories show AST and ALT 1.5 times normal, normal bilirubin and alkaline phosphatase, and a normal CBC. Your next step is: • Reassurance • CT scan of the liver • Hepatitis serologies • ANA and serum protein electrophoresis • Alcohol counseling

  32. Liver Disease • Autoimmune hepatitis • Distribution 3:1 F:M • Peaks 10-20 years, 50 years • Presentation • Chronic • Fulminant • 1/3 with another autoimmune disorder

  33. Liver Disease • Autoimmune hepatitis • Fatigue • Jaundice • Anorexia • Myalgia

  34. Liver Disease • Autoimmune hepatitis • Ast Alt ≈ 500 (>1000) • ANA >1:80 • ASMA > 1:80 • LKM1 >1:80 • Gamma globulin > 1.5x normal

  35. Liver Disease • Autoimmune hepatitis • Biopsy • Interface hepatitis • Plasma cells

  36. Liver Disease • Autoimmune hepatitis • Treatment • Prednisone / imuran • 80% remission • 2 years • Relapse in 50% • Retreat relapsers • 90% mortality untreated

  37. Your patient, a 58 year old woman, presents with one month of pruritus. She has no significant past medical or exposure history, no recent travel or new pets. Examination shows xanthomas and excoriations, and otherwise is normal. Labs show AST and ALT twice normal, and alkaline phosphatase of 450 U/L, total bilirubin of 1.2 mg/dL. The your next step should be: • Reassurance • CT scan of the liver • Hepatitis serologies • Liver biopsy • Anti mitochondrial antibody

  38. Liver Disease • Primary biliary cirrhosis • Small bile duct • 9:1 M:F • Age 40-60 • Elevated alkaline phosphatase • Pruritus / fatigue • AMA > 1:40 • Ursodeoxycholic acid 12 -15 mg/kg • Osteoporosis

  39. Your patient, a 24 year old male with a 10 year history of ulcerative colitis, presents for a routine evaluation. His colitis has been under control with Asacol, and he has no other significant medical issues. Examination is unremarkable. Laboratories show AST and ALT twice normal, Alkaline phosphatase 450, total bilirubin of 1.4 mg/dL, and a normal CBC. Your next step is: • Reassurance • CT scan of the liver • Hepatitis serologies • ERCP • Liver biopsy

  40. Liver Disease • Primary sclerosing cholangitis • Medium and large duct disease • 80% associated with ulcerative colitis • Increased alkaline phosphatase • Dominant strictures • Cholangiocarcinoma / colon ca • Osteoporosis • No effective treatment

  41. Your patient presents for routine follow up. He is a 53 year old lawyer with a past medical history of hypertension, elevated cholesterol and type 2 diabetes. He is on therapy for all three diseases. Examination is normal except for obesity. Labs show a normal AST, ALT of 60 U/L, normal alkaline phosphatase and bilirubin. Previous labs have been normal. Your next step should be: • Reassurance • CT scan of the liver • Hepatitis serologies • Liver biopsy • Repeat labs in 3 months

  42. Liver Disease • NASH • Fatty liver – cirrhosis • Obesity • DM • Hyperlipidemia • TPN • ALT>AST <200 • Diagnosis of exclusion

  43. Liver Disease • NASH • Treatment • Weight loss • Control of diabetes / lipids • Gastric bypass • PPAR-g agents

  44. Liver Disease • Alcoholic liver disease • Alcoholic liver disease • 80 g / d men • 40 g / d women • AST 2x ALT <300

  45. Liver Disease • Alcoholic liver disease • Alcoholic hepatitis • Elevated AST>ALT bilirubin INR WBC • Discriminant function >35 • 4.6[Pt-Ptcontrol] + bil (mg/dL) • Neutrophils on biopsy • Treatment • Prednisone / pentoxyphylline / TNF a agents

  46. You are seeing a new patient, a 35 year old male. He complains of some fatigue, but otherwise is in good health. Examination is normal. His family history includes cirrhosis in an uncle and CAD. Labs show normal liver enzymes, a ferritin of 750 mg/L, and iron saturation of 88%. Your next step is: • Reassurance • CT scan of the liver • HFE gene study • Hepatitis serologies • Liver biopsy with quantitative iron level

  47. Liver Disease • Hereditary Hemochromatosis • Most common inherited disorder in Europeans • C282Y H63D • Autosomal recessive • Ferritin elevation • 400 • Iron saturation • 50%

  48. Liver Disease • Hereditary Hemochromatosis • Diabetes • Cardiomyopathy • Arthritis PIP/DIP

  49. Liver Disease • Hereditary Hemochromatosis • Ferritin > 1000 / elevated AST – biopsy • No role for iron index

  50. Your patient , a 35 year old male with hereditary hemochromatosis (C282Y/C282Y) presents asking about therapeutic options. His labs showed AST and ALT twice normal, ferritin of 1300 mg/L, iron saturation of 92%. Liver biopsy showed minimally increased fibrosis. Your next step is: • Reassurance • Chelation with desferroximine • Weekly therapeutic phlebotomy • Low iron diet and observation • Penicillamine therapy

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